Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, Lodz, 90-151, Poland.
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Sw. Teresy 8, Lodz, 91-348, Poland.
Environ Toxicol. 2018 Jun;33(6):695-705. doi: 10.1002/tox.22558. Epub 2018 Apr 16.
Hexachloronaphthalenes (HxCNs) are the most toxic congeners of polychlorinated naphthalenes, a group of compounds lately included into the list of persistent organic pollutants (POPs). This study presents the effects of 90-day intragastric administration of HxCN to female Wistar rats at doses of 0.03, 0.1, and 0.3 mg/kg body weight. The study examined selected parameters of the heme synthesis pathway, oxidative stress, hepatic cytochromes level, and basic hematology indicators. A micronucleus test was also performed. The subchronic exposure of rats to HxCN resulted in disruption of heme biosynthesis, hematological disturbances, and hepatotoxicity. The highest dose of HxCN inhibited aminolevulinic acid dehydratase (ALA-D) and uroporphyrinogen decarboxylase (URO-D). Accumulation of higher carboxylated porphyrins in the liver and increased excretion of 5-aminolevulinic acid in the urine was observed after a dose of 0.1 mg/kg body weight. The most sensitive effect of HxCN in rats was very strong induction of hepatic CYP1A1 activity, which was observed after the lowest dose. The highest dose of HxCN induced significant thrombocytopenia, thymic atrophy and hepatotoxicity, expressed as hepatomegaly and hepatic steatosis.
六氯萘（HxCNs）是多氯萘中最具毒性的同系物，多氯萘是最近被列入持久性有机污染物（POPs）名单的一组化合物。本研究对雌性 Wistar 大鼠进行了为期 90 天的胃内给药，剂量分别为 0.03、0.1 和 0.3 mg/kg 体重，研究了 HxCN 的作用。研究了血红素合成途径、氧化应激、肝细胞色素水平和基本血液学指标的选定参数。还进行了微核试验。大鼠亚慢性暴露于 HxCN 会破坏血红素生物合成、血液紊乱和肝毒性。最高剂量的 HxCN 抑制了氨基酮戊酸脱水酶（ALA-D）和尿卟啉原脱羧酶（URO-D）。在 0.1 mg/kg 体重剂量下，观察到肝脏中更高的羧基化卟啉的积累和尿液中 5-氨基酮戊酸的排泄增加。HxCN 在大鼠中最敏感的作用是强烈诱导肝 CYP1A1 活性，这在最低剂量下就观察到了。最高剂量的 HxCN 诱导了明显的血小板减少症、胸腺萎缩和肝毒性，表现为肝肿大和肝脂肪变性。
